WO2020090226A1

WO2020090226A1 - Discharge control device, discharge device, discharge method, and program

Info

Publication number: WO2020090226A1
Application number: PCT/JP2019/035103
Authority: WO
Inventors: 尚存柴田; 元毅沖仲; 孝介倉知
Original assignee: キヤノン株式会社
Priority date: 2018-10-31
Filing date: 2019-09-06
Publication date: 2020-05-07
Also published as: JP2020068722A

Abstract

The discharge device according to the present application is characterized by comprising a discharge unit that discharges a first droplet and a second droplet that include different cells into a pore on the skin of a living body, and an adjustment unit that adjusts impact positions of the first droplet and the second droplet in the pore that are discharged from the discharge unit.

Description

Discharge control device, discharge device, discharge method, and program

The disclosure of the present specification relates to a discharge control device, a discharge device, a discharge method, and a program.

With the worldwide increase in population in recent years, the number of men and women suffering from thinning hair is increasing. Therefore, a hair regeneration technique is currently drawing attention as one of the treatment methods for thinning hair.

In the treatment of thinning hair, the flow of hair is important in order to make the hair look natural after treatment. Therefore, in the hair regrowth technique, it is necessary to consider the hair growth direction after regrowth. Since the hair growth direction is determined by the positional relationship between the epithelial cells and mesenchymal cells that form the hair, controlling the positional relationship between the two cells in the pores (within the pores) of the hair The extension direction of can be controlled.

As a technique for controlling the positional relationship of a plurality of cells, a technique is known in which cells are repeatedly discharged onto a flat culture bed and the cells are stacked (Patent Document 1).

Japanese Patent No. 5483488

However, controlling the arrangement of multiple cells within one pore was not known.

One of the objects of the disclosure of the present specification is to provide an ejection device capable of desirably disposing a plurality of droplets ejected in one hole.

It should be noted that the present invention is not limited to the above-mentioned object, and it is also possible to achieve operational effects that are obtained by the respective configurations shown in the modes for carrying out the invention to be described later and that cannot be obtained by conventional techniques. It can be positioned as one of the other purposes.

An ejection control device disclosed in the present specification includes an instruction unit that issues an instruction to eject droplets to an ejection unit that ejects a first droplet and a second droplet containing different cells, and the ejection unit. An adjusting unit that adjusts the landing positions of the first droplet and the second droplet, which are discharged from the inside of the hole into the hole of the living body. And

According to the disclosure of the present specification, it is possible to desirably arrange a plurality of droplets ejected in one hole.

The figure which shows an example of a structure of the discharge device which concerns on this embodiment. The figure which shows an example of the extension direction of the hair in the hole which concerns on this embodiment. The figure which shows an example of the extension direction of the hair in the hole which concerns on this embodiment. The figure which shows an example which discharges a droplet in a perforation using the discharge device which concerns on this embodiment. The figure which shows an example which discharges a droplet in a perforation using the discharge device which concerns on this embodiment. The figure which shows an example which discharges a droplet in a perforation using the discharge device which concerns on this embodiment. The figure which shows an example which discharges a droplet in a perforation using the discharge device which concerns on this embodiment. The figure which shows an example which discharges a droplet in a perforation using the discharge device which concerns on a present Example.

Hereinafter, embodiments of a discharge device disclosed in the present specification will be described in detail with reference to the accompanying drawings. However, the scope of the invention is not limited to the illustrated examples.

<Embodiment>
The ejection device according to the present embodiment is a device that ejects droplets containing cells into a plurality of holes perforated in the skin of a living body. For example, it can be used for the purpose of regenerating hair follicles and hair by ejecting droplets containing epithelial cells and mesenchymal cells into the holes perforated in the human scalp.

The following are merely examples for explaining the processing method of the ejection device, and the disclosure of the present specification is not limited to the embodiments.

An embodiment of a discharge device disclosed in the present specification will be described with reference to the drawings.

FIG. 1 is a diagram showing an example of the configuration of a discharge device.

The ejection device 1 includes an ejection unit 2, an X scan stage 3, a Y scan stage (not shown), a Z scan stage 4, a rotating unit 5, an ejection control device 100, and a detection device 12. .. The ejection control device 100 includes an instruction unit 6, a position control unit 7, a rotation control unit 8, and a position detection unit 11.

The ejection unit 2 ejects droplets 9 containing cells into the perforations 101 formed in the scalp.

The perforations 101 are cylindrical portions formed on the skin of the base body 10, and indicate pores or perforated holes formed in the base body 10. The base 10 is, for example, the skin of a living body such as a human or a mouse. The perforated holes are formed in the epidermis and part of the dermis by using a processing device such as a laser. The opening shape of the perforations 101 may be circular or rectangular.

The droplet 9 is a generic term for a first droplet 901 containing mesenchymal cells and a second droplet 902 containing epithelial cells. The mesenchymal cells and epithelial cells contained in the two droplets are cells that are at least necessary for forming a hair follicle primordium having a hair regenerating ability.

Mesenchymal cells indicate at least one of cells derived from mesenchymal tissue and cells obtained by culturing the cells. For example, it can be obtained from hair papilla cells, dermal sheath cells, various pluripotent cells, and the like.

The epithelial cell indicates at least one of cells derived from epithelial tissue and cells obtained by culturing the cells. For example, it can be obtained from the outermost layer of the outer root sheath, epithelial cells of the hair matrix, various pluripotent cells, and the like.

The hair follicle primordium is a tissue that is a base of hair follicles and is composed of a cell group including the above-mentioned mesenchymal cells and epithelial cells. For example, epithelial cells and mesenchymal cells are ejected to the perforation 101, and the hair follicle primordium composed of the two cells forms a hair follicle. Then, hair having a hair shaft is formed and elongated from the formed hair follicle. That is, the hair follicle primordia form the hair follicle and are the basis for the regenerated hair.

The ratio of these cell numbers is preferably 1: 1 from the viewpoint of hair regeneration, and if the total cell number of mesenchymal cells and epithelial cells is about 1000 to 10000, it forms a hair follicle primordium. be able to. The ratio of the number of cells and the number of cells are not necessarily the above values.

In addition, the droplet 9 may include a medium for each cell, nutrients necessary for cell survival and growth, and auxiliary substances such as antibiotics and hormones.

The above-mentioned “cell” may be a single substance or an aggregate including a plurality of cells such as a cell group. In this embodiment, an aggregate including a plurality of cells such as a cell group is referred to as a cell.

A thermal ink jet head, a piezoelectric ink jet head, an electrostatic ink jet head, a compressed air jet dispenser, or the like can be used as the ejection unit 2, but any element can be used as long as it can eject droplets containing cells. Further, it is desirable that the ejection portion 2 has an opening capable of ejecting a droplet of 1 to 500 nl, but the invention is not limited to this.

Further, the number of ejection portions (openings) forming the ejection portion 2 may be changed depending on the number of droplets containing cells to be ejected. For example, as shown in FIG. 1, a first ejection portion 201 that ejects a first droplet 901 containing mesenchymal cells necessary for hair regeneration and a second droplet 902 containing epithelial cells are provided. It may be configured to include two ejection portions, the second ejection portion 202 for ejecting. The positions of the first ejecting unit 201 and the second ejecting unit 202 may be positions capable of ejecting droplets to the perforations 101, but when ejecting droplets continuously, the ejecting unit 2 It is desirable that they are arranged in the scan direction.

In the present embodiment, the number of ejection portions (openings) included in the ejection portion 2 is two, but the number is not limited to this. For example, if there are three types of droplets containing cells to be ejected, three ejection parts may be provided. Further, even when there are two types of liquid droplets containing cells to be discharged, three or more discharging portions may be provided. For example, three or more ejection portions that eject droplets containing mesenchymal cells and ejection portions that eject droplets containing epithelial cells may be provided alternately. Furthermore, when four ejection portions are provided, three ejection portions ejecting droplets containing mesenchymal cells and one ejection portion ejecting droplets containing epithelial cells are used. The number of discharge parts may be inclined. Further, even if there is only one type of liquid droplet containing cells to be discharged, it is possible to discharge continuously by providing a plurality of discharging portions.

Since the droplets 9 are ejected to the living body, in consideration of the movement and shape change of the base (scalp) 10 or the exudation of body fluid, the ejection unit 2 ejects a plurality of droplets at a speed of 500 droplets / minute or more. However, the present invention is not limited to this.

The X scan stage 3, the Y scan stage (not shown), and the Z scan stage 4 are each connected to the ejection unit 2. As a result, the ejection unit 2 can move in the X direction, the Y direction, and the Z direction. The rotating unit 5 is also connected to the discharge unit 2. As a result, the ejection unit 2 can rotate in the XZ plane and the XY plane. That is, the ejection unit 2 can move in accordance with the position of the perforation 101 formed in the scalp 100 by driving on a three-dimensional plane according to the scan stage and rotational driving according to the rotating unit 5. When the ejection unit 2 is composed of a plurality of ejection units, each ejection unit may be independently drivable.

The ejection control unit 100 is a computer for controlling the operation of the ejection unit 2, and internally includes a CPU, a memory, an I / O port, and the like.

An operation program of the ejection unit 2 is stored in the memory. The program for executing various processes related to the ejection of the droplet 9 may be stored in the memory like other operation programs, or may be loaded from the outside to the memory via the network. Alternatively, the program may be loaded into the memory via a computer-readable recording medium.

The I / O port of the ejection control unit 100 is connected to an external device such as an external computer or a network. The ejection control unit 100 can input and output the ejection conditions of the droplets 9 such as the ejection speed, the amount of ejected droplets, and the ejection timing with an external device via the I / O port. The CPU included in the ejection control unit 100 includes control units such as an instruction unit 6, a position control unit 7, a rotation control unit 8, and a position detection unit 11. These are connected to the ejection unit 2, each scan stage, the rotating unit 5, the detection device 12, and the like, and can exchange electric signals. The ejection control unit 100 controls the operation of each of these units, and executes the processing relating to the overall ejection of the droplet 9 including the scanning of the ejection unit, the ejection conditions, the imaging of the detection device 12, and the like.

The instructing unit 6 issues an ejection instruction to the ejection unit 2 when the ejection unit 2 whose posture and position are controlled by the position control unit 7 and the rotation control unit 8 reaches a target position. As a result, droplets 9 containing cells are ejected to the perforations 101. That is, the instruction unit 6 issues a droplet ejection instruction to the ejection unit 2 that ejects the first droplet 901 and the second droplet 902 containing different cells.

Further, the instruction unit 6 controls the ejection speed of ejected droplets, the amount of ejected droplets, the ejection timing, and the like. The ejection speed, the amount of ejected liquid droplets, the ejection timing, and the like are controlled by a voltage application waveform, and the waveform is determined in advance by ejection observation and landing measurement performed by another device (not shown). In addition, when the number of cells contained in one shot is less than the specified amount, the discharge instruction may be performed so as to discharge the same hole a plurality of times.

The position control unit 7 and the rotation control unit 8 control the attitude and position of the ejection unit 2, and control (adjust) the ejection direction and the landing position of the droplet 9 ejected by the ejection unit 2. Specifically, the position controller 7 controls the movement of the position of the ejection unit 2 connected to the X scan stage 3, the Y scan stage (not shown), and the Z scan stage 4. The rotation control unit 8 controls the rotation drive of the discharge unit 2 by the rotation unit 5. By these, the ejection portion 2 is aligned (aligned) with the hole 101 so that the droplet 9 can be ejected.

In addition, when the ejection unit 2 includes a plurality of ejection units, the position control unit 7 and the rotation control unit 8 may control the plurality of ejection units to perform different movements. For example, when the ejection unit 2 includes two ejection units, the rotation control unit 8 controls the rotation so that each ejection unit ejects droplets at different angles with respect to one hole. Moreover, you may control so that all the discharge parts may move the same. Furthermore, it is also possible to perform control so that all the ejection units move in the same manner, and then apply different control only to the ejection units for which fine adjustment is desired.

The position control unit 7 and the rotation control unit 8 can control (adjust) the landing positions of the first droplet 901 and the second droplet 902 for each hole.

That is, the position control unit 7 and the rotation control unit 8 respectively adjust the landing positions of the first droplet and the second droplet ejected from the ejection unit 2 into one hole opened in the skin of the living body. It corresponds to an example of a possible adjustment unit.

The position control unit 7 and the rotation control unit 8 may be configured to determine the control condition of the ejection unit 2 in cooperation with a hole processing device (laser, needle-shaped protrusion, etc.) not shown.

The position detection unit 11 performs image processing on the image captured by the detection device 12, converts the position of the ejection unit 2 and the position of the perforation 101 to be landed into coordinate data, and detects the coordinate data. Further, the position of the droplet discharged into the hole after landing is detected. Specifically, for example, a range of pixel values that can be assumed when the liquid droplets are inside the hole is designated in advance, and the liquid droplets are recognized when the pixel values fall within the range as a result of image processing. Specify the coordinates. Further, the detection device 12 may be a laser device including a light receiving sensor or the like, in addition to the image pickup device that picks up an image as described above. In this case, the presence or absence of droplets may be detected by laser scanning the holes before and after the droplets are ejected. The detection method is not limited to the above.

Next, an example in which the hair elongation direction is determined by the positional relationship between the mesenchymal cells and epithelial cells that form the hair follicle primordia will be described with reference to FIGS. 2A and 2B. 2A and 2B show an example in which the positional relationship between the droplet containing the mesenchymal cells and the droplet containing the epithelial cells ejected by the ejecting unit 2 is different in the perforation 101. 2A and 2B, the wall surface on the right side of the central axis (dotted line) of the perforation 101 is the right wall surface, and the left wall surface is the left wall surface, as shown in FIGS. 2A and 2B. The opening side of 101 is defined as the top.

FIG. 2A shows a state in which mesenchymal cells 110 are arranged in the central portion of the bottom of the perforation 101, and epithelial cells 120 are arranged so as to overlap therewith. Specifically, the position detection unit 11 converts the image captured by the detection device 12 into coordinate data, and detects the position of the perforation 101 to be ejected. Then, based on the position information acquired from the detection device 12, the position control unit 7 and the rotation control unit 8 align the ejection unit 2 with the hole 101 so that the droplet 9 can be ejected. The method of alignment is not limited to the above, and for example, a configuration may be employed in which an alignment mark or the like is marked in advance on a portion to be ejected and the alignment is detected to perform alignment based on the coordinate data of the alignment mark. Then, when the instruction unit 6 issues an ejection instruction to the ejection unit 2, the first ejection unit 201 ejects the first droplet 901 containing the mesenchymal cells 110 to the central portion of the bottom of the perforation 101.

Then, the second ejection unit 202 ejects the second droplet 902 containing the epithelial cells 120 at the same coordinates as the ejection position of the first ejection unit 201. That is, the instruction unit 6 issues an ejection instruction to eject the first droplet 901 at the first time and eject the second droplet 902 at the second time later than the first time. As described above, the epithelial cells 120 are arranged on the mesenchymal cells 110. In other words, the ejection unit 2 ejects the two droplets so that the second droplet 902 is closer to the opening of the perforation 101 than the first droplet 901 in the perforation 101. In this case, the extending direction of the bristles is perpendicular to the opening of the perforation 101.

On the other hand, FIG. 2B shows a state in which the mesenchymal cells 110 are arranged to the right of the center of the bottom of the perforation 101, and the epithelial cells 120 are arranged diagonally to the upper left. Specifically, the position detection unit 11 converts the image captured by the detection device 12 into coordinate data, and detects the position of the perforation 101 to be ejected. Then, based on the position information obtained from the detection device 12, the position control unit 7 and the rotation control unit 8 align the ejection unit 2 with the perforation 101 at a position where the droplet 9 can be ejected. .. Then, the instruction unit 6 issues an ejection instruction to the ejection unit 2 so that the first ejection unit 201 ejects the first droplet 901 containing the mesenchymal cells 110 to the right side from the central portion of the bottom of the perforation 101. Discharge. After that, the alignment is performed similarly, and the second ejection portion 202 ejects the second droplet 902 containing the epithelial cells 120 from the central portion of the bottom portion of the perforation 101 to the left side. That is, the first droplet 901 and the second droplet 902 are landed on the side walls of the perforation 101 that face each other.

As described above, the epithelial cell 120 is arranged diagonally to the upper left of the mesenchymal cell 110. In this case, the hair extension direction is the upper left direction.

As described above, as shown in FIGS. 2A and 2B, controlling the positional relationship between the first droplet 901 containing the mesenchymal cells 110 and the second droplet 902 containing the epithelial cells inside the perforation 101. The hair extension direction can be controlled by.

Next, specific control when ejecting the first droplet 901 and the second droplet 902 into the perforation 101 will be described with reference to FIGS. 3A, 3B, 4A, and 4B. Note that the control described below shows a case where the extension direction of the bristles is controlled to the upper left direction as shown in FIG. 2B, but the position where the droplets are arranged is not limited to this, and various positions that achieve the desired extension direction are shown. Droplets can be placed on. That is, the two droplets do not necessarily have to be discharged to the side walls of the perforation 101 that face each other.

In FIGS. 3A and 3B, a first droplet 901 containing mesenchymal cells 110 is arranged on the right wall surface inside the perforation 101 while scanning the first ejection unit 201 and the second ejection unit 202 in the same direction. However, an example of arranging the second droplet 902 containing the epithelial cells 120 on the left wall surface is shown.

The ejection unit 2 ejects the droplet 9 while moving in any direction of the XYZ axes by the connected X scan stage 3, Y scan stage, and Z scan stage (not shown). Further, the instructing unit 6, the position control unit 7, and the rotation control unit 8 control the ejection speed of the ejected droplet 9 or the scanning speed of the ejection unit 2 and the ejection angle, so that the droplet containing cells can be arbitrarily set in the hole. Can be landed at the position.

FIG. 3A shows an example in which the first droplet 901 containing the mesenchymal cells 110 is arranged on the right wall surface inside the perforation 101. Specifically, the position detection unit 11 converts the image captured by the detection device 12 into coordinate data, and detects the position of the perforation 101 to be ejected. Then, based on the position information obtained from the detection device 12, the position control unit 7 and the rotation control unit 8 align the ejection unit 2 with the perforation 101 at a position where the droplet 9 can be ejected. .. Here, the ejection portion 2 is scanned in the positive direction of the X axis. Then, the instruction unit 6 issues an ejection instruction to the ejection unit 2 so that the first droplet 901 containing the mesenchymal cells 110 is landed on the right wall surface of the perforation 101.

FIG. 3B shows an example of a state in which the second droplet 902 containing the epithelial cells 120 is arranged on the left wall surface inside the perforation 101 after performing the process of FIG. 3A. Specifically, the position controller 7 controls the scanning speed of the ejection unit 2 in the positive direction of the X-axis to be smaller than that when the first droplet 901 is ejected. Furthermore, the rotation control unit 8 also rotates the rotation unit 5 to adjust the droplet trajectory of the second discharged droplet 902 containing epithelial cells. Droplets can be landed anywhere in the hole, here the left wall, by combining either or both of these means.

4A and 4B show an example of an ejection method in the case where the first droplet 901 and the second droplet 902 are arranged on the left and right sides in the perforation 101 with higher throughput, similarly to FIGS. 3A and 3B. Is. Specifically, the direction of scanning the ejection unit 2 when ejecting the first droplet 901 in the X-axis direction and the direction of scanning the ejection unit 2 when ejecting the second droplet 902 are the same axis. Reverse in direction. In the present embodiment, the scan direction that is reversed when ejecting the second droplet 902 is the X-axis direction, but the axis direction that is reversed is not limited to the above. For example, when a plurality of holes are arranged in the Y-axis direction and the droplet 9 is discharged while scanning in the Y-axis direction, the Y-axis is discharged after the first droplet 901 is discharged to one hole. The second droplet 902 is discharged by reversing the scanning direction.

Since FIG. 4A performs the same control as FIG. 3A, its description is omitted.

FIG. 4B shows an example of a state in which the second droplet 902 containing the epithelial cells 120 is arranged on the left wall surface inside the perforation 101 after the treatment of FIG. 4A. Specifically, the position control unit 7 reverses the scanning direction of the ejection unit 2 to the negative direction of the X-axis, and the rotation control unit 8 rotates the rotating unit 5 to adjust the droplet orbit to include epithelial cells. The second discharged droplet 902 is landed on the left wall surface.

In this way, by adjusting the direction and the order in which the droplets containing cells are landed, the droplets are arbitrarily arranged in the perforations 101, and the hair extension direction is controlled.

Based on the above, it is possible to desirably arrange a plurality of droplets discharged into one hole. Further, by arranging the plurality of droplets desirably, it is possible to control the extension direction of the hair formed from the cells contained in the plurality of droplets to a desired direction. Further, the positional relationship between the respective droplets can be maintained even after the ejection of the two droplets is completed.

Further, by ejecting the first droplet 901 and the second droplet 902 while scanning the ejection unit 2 so as to reciprocate with respect to the perforation 101, a plurality of droplets can be moved to desired positions within the perforation 101. It is possible to dispose the droplets and to discharge the droplets with higher throughput.

Further, by causing the first droplet 901 and the second droplet 902 to land on the opposite wall surfaces in the perforation 101, the position of the droplet first ejected into the perforation 101 is later ejected. It is possible to reduce the possibility that the liquid droplets will change. More specifically, it is possible to reduce the possibility that the droplets are mixed with each other or the cells in the droplets are agitated by the kinetic energy of the droplets.

It should be noted that the droplets discharged first to the perforations 101 do not necessarily have to land on the wall surface. As long as the subsequently ejected droplets land on the wall surface, the previously ejected droplets can be landed in a state where the kinetic energy is small, so that the above effect can be achieved. That is, the landing position may be adjusted so that at least the second liquid droplet 902 of the first liquid droplet 901 and the second liquid droplet 902 land on the side wall of the perforation 101.

Furthermore, by making the viscosity of the first droplet 901 higher than the viscosity of the second droplet 902, it is possible to further suppress mixing and stirring of cells. The viscosity of each droplet is preferably 10 mPa · sec or more and 70 mPa · sec or less. More preferably, it is 20 mPa · sec or more and 60 mPa · sec or less. More preferably, it is 30 mPa · sec or more and 50 mPa · sec or less. The liquid viscosity as described above makes it easier to control the landing position. Further, it is possible to reduce the possibility of causing clogging during ejection. Further, by making the discharge speed of the second droplets slower than the discharge speed of the first droplets 901, it is possible to further suppress mixing and stirring of the droplets.

Hereinafter, preferred embodiments of the ejection device disclosed in the present specification will be described with reference to the drawings.

However, the dimensions, materials, shapes, and their relative arrangements of the components described below should be appropriately changed depending on the configuration of the apparatus to which the invention is applied and various conditions. The same applies to the specific droplet discharge amount and viscosity, and the member control position and speed according to the embodiment. That is, the scope of the disclosure of the present specification is not intended to be limited to the following description.

[Example 1]
In this example, a jet dispenser (Jet Spotter: manufactured by Musashi Engineering Co., Ltd.) is used to eject droplets containing cells into holes formed in the skin collected from a mouse. Note that this example is in accordance with the steps shown in FIGS. 3A and 3B of the above-described embodiment.

First, the collected mouse skin is separated into an epithelial layer and a dermal layer, and epithelial stem cells and mesenchymal stem cells are taken out from the respective layers. Then, after culturing the respective cells, they are mixed with the basic medium to obtain a suspension for ejection.

Considering the size of cells, the nozzle (opening) diameter of the discharge part is 150 μm. As for the ejection amount, 30 nL is ejected as one drop in consideration of the volume of the perforations 101. The concentration is adjusted so that the total number of cells contained in 30 nL is 5000. Bubbling is performed at an appropriate timing so that cells do not settle in the nozzle. The liquid viscosity of the ejection suspension is adjusted to 50 mPa · sec.

The ejection waveform is adjusted so that the ejection speed of the droplets ejected from the jet dispenser is 5 m / sec.

FIG. 5 shows an example in which droplets containing cells according to this embodiment are discharged to the perforations 101. The opening diameter of the perforations 101 formed by the processing device in the pre-discharge step is 500 μm and the depth is 1000 μm. On the other hand, the diameter of the droplet is about 190 μm.

First, the first droplet 901 containing the mesenchymal cells 110 is ejected to the perforation 101. Then, the second droplet 902 containing the epithelial cells 120 is ejected. At this time, the ejection unit 2 is moved along the X axis and ejected in consideration of the droplet trajectory so as to land on the bottom of the hole. In the present embodiment, the landing coordinates are determined so that the angle α formed by the line connecting the mesenchymal cells 110 and the epithelial cells 120 with the drilling direction is 30 °.

The trajectory of the droplet is determined by the combination of the velocity in the Z direction and the velocity in the X direction. The speed in the Z direction is adjusted by the ejection speed, and the speed in the X direction is adjusted by the scan speed of the head. Since the flight time of the droplet can be calculated from Gap up to the desired coordinates (X, Z) in the hole and the velocity in the Z direction, the timing of droplet ejection from the head is determined based on this.

In this embodiment, the center of the bottom of the hole is set to 0 in the XZ coordinate system, and the first droplet 901 containing the mesenchymal cells 110 is landed at the position (X, Z) = (57 μm, 0 μm). , And the scanning speed in the X direction is 1.3 m / sec.

The designed landing position of the second droplet 902 containing the epithelial cells 120 is (X, Z) = (− 153 μm, 166 μm). In order to prevent the first droplet 901 and the second droplet 902 from being mixed after landing, the ejection portion 2 is inclined by 10 ° in order to suppress the ejection speed of the second droplet 902 in the X direction to be small. To do. Therefore, the scanning speed in the X direction when the second droplet 902 is landed is about 0.8 m / sec.

Hair growth can be confirmed by culturing mesenchymal stem cells and epithelial interstitial cells within the scalp perforation of mice after cell injection and observing the treated area 3 weeks later. In addition, the hair cycle can also be confirmed.

[Example 2]
In this embodiment, ejection is performed by adjusting the liquid viscosity of the second droplet 902 containing the epithelial cells 120 to be lower than that of the first droplet 901. Specifically, the liquid viscosity of the first droplet 901 is 50 mPa · sec, and the liquid viscosity of the second droplet 902 is 30 mPa · sec.

The perforation 101 for ejecting cells has the same form as that of the first embodiment, and the landing coordinates are determined so that the angle α formed by the line connecting the mesenchymal cells 110 and the epithelial cells 120 with the perforation direction is 0 °. ..

The center of the bottom of the hole is set to 0 in the XZ coordinate system, and the first droplet 901 containing the mesenchymal cells 110 is moved in the X direction so as to land at the position (X, Z) = (− 153 μm, 0 μm). The scan speed is 1.7 m / sec. Subsequently, the second droplet 902 containing the epithelial cells 120 is set to have a scan speed in the X direction of 1.7 m / sec so that the second droplet 902 will land at the position of (X, Z) = (− 153 μm, 192 μm). ..

According to the present embodiment, the liquid viscosity of the second droplet 902 is made lower than the liquid viscosity of the first droplet 901, and the first droplet 901 and the second droplet 901 are discharged. More hair growth can be confirmed than when the liquid viscosity of 902 is the same.

[Example 3]
This example is based on the steps shown in FIGS. 4A and 4B of the above-described embodiment, and includes a first droplet 901 containing mesenchymal cells 110 and a second liquid containing epithelial cells 120. The X-direction scanning direction when ejecting the droplet 902 is reversed to eject the droplet. Both liquid viscosities are adjusted to 50 mPa · sec.

The perforation 101 for ejecting cells has the same form as in Example 1, and the landing coordinates are determined so that the angle α formed by the line connecting the mesenchymal cell 110 and the epithelial cell 120 with the perforation direction is 60 °. ..

The center of the bottom of the hole is set to 0 in the XZ coordinate system, and the first droplet 901 including the mesenchymal cells 110 is scanned in the X direction so as to land at the position (X, Z) = (13 μm, 0 μm). The speed is 0.7 m / sec. Then, the second droplet 902 containing the epithelial cells 120 has a scan speed in the X direction of -1.7 m / sec so as to land at the position of (X, Z) = (-153 μm, 96 μm). To do.

According to this embodiment, the first droplet 901 and the second droplet 902 are scanned in the same scan by reversing the scan direction when ejecting the second droplet 902 and ejecting the droplet. It is possible to confirm more hair growth than when ejected in one direction.

As described above, according to the first to third embodiments, it is possible to desirably arrange a plurality of liquid droplets discharged into one hole, and it is also possible to improve the hair regeneration efficiency.

(Other embodiments)
The disclosure of the present specification provides a program that implements one or more functions of the above-described embodiments to a system or apparatus via a network or a storage medium, and one or more processors in a computer of the system or apparatus provide the program. Can also be realized by a process of reading and executing. It can also be realized by a circuit (for example, ASIC) that realizes one or more functions.

The discharge control device in the above-described embodiment may be realized as a single device, or may be a mode in which a plurality of devices are communicably combined with each other to execute the above-described processing, and both are in the embodiment of the present invention included. The above-described processing may be executed by a common server device or server group. It suffices that the plurality of devices constituting the discharge control device and the discharge control system can communicate at a predetermined communication rate, and they do not have to exist in the same facility or in the same country.

In the embodiments disclosed in the present specification, a software program that realizes the functions of the above-described embodiments is supplied to a system or apparatus, and the computer of the system or apparatus reads out the code of the supplied program. Including the form of executing.

Therefore, the program code itself installed in the computer to implement the processing according to the embodiment by the computer is also one of the embodiments of the present invention. Further, based on the instructions included in the program read by the computer, the OS or the like running on the computer may perform some or all of the actual processing, and the processing may also realize the functions of the above-described embodiments. ..

Further, the disclosure of the present specification is not limited to the above-described embodiments, and various modifications (including organic combinations of the examples) are possible based on the gist of the disclosure of the present specification. It is not excluded from the scope of the disclosure herein. That is, all configurations that combine the above-described examples and the modifications thereof are also included in the embodiments disclosed in the present specification.

This application claims priority on the basis of Japanese patent application Japanese Patent Application No. 2018-205559 filed on October 31, 2018, and the entire contents of the description are incorporated herein.

1 Ejection Device 2 Ejection Unit 3 X Scan Stage 4 Z Scan Stage 5 Rotating Unit 6 Pointing Unit 7 Position Control Unit 8 Rotation Control Unit 9 Droplet 10 Substrate (Skin)
11 Position Detection Unit 110 Mesenchymal Cell 120 Epithelial Cell

Claims

An instructing unit for instructing ejection of droplets to an ejecting unit that ejects a first droplet and a second droplet containing cells different from each other;
An adjusting unit that adjusts the landing position of at least one of the first droplet and the second droplet discharged from the discharging unit into one hole opened in the skin of the living body;
A discharge control device comprising:
The ejection control device according to claim 1, wherein the adjustment unit controls the landing position by controlling the ejection unit.
The ejection control device according to claim 2, wherein the adjustment unit includes a position control unit that adjusts a position of the ejection unit with respect to the hole.
The ejection control device according to claim 2, wherein the adjustment unit includes a rotation control unit that adjusts an angle of the ejection unit to control an ejection direction of the droplet.
The ejection control device according to claim 1, further comprising a detection unit that detects a position of the hole and a landing position of the first droplet and the second droplet. ..
The ejection unit according to claim 5, wherein the detection unit detects a position of the hole and a landing position of the first droplet and the second droplet based on an image captured by a detection device. Control device.
The ejection unit according to claim 5 or 6, wherein the adjusting unit adjusts the landing position by aligning the ejection unit based on position information indicating the position of the hole detected by the detection unit. Control device.
8. The speed is controlled by an adjusting unit so that the ejection speed of the first droplets is higher than the ejection speed of the second droplets. Discharge control device.
The ejection control device according to any one of claims 1 to 8, wherein a rate at which the ejection unit ejects a plurality of liquid droplets continuously is 500 drops / minute or more.
The adjusting unit adjusts the landing position so that at least one of the first liquid droplet and the second liquid droplet that is ejected later land on the side wall of the hole. Item 10. The discharge control device according to any one of Items 1 to 9.
11. The ejection according to claim 10, wherein the adjustment unit adjusts the landing position so that the first droplet and the second droplet land on the side walls of the hole that face each other. Control device.
The instructing unit causes the ejecting unit to eject the first droplet into the hole at a first time, and the second liquid into the hole at a second time later than the first time. The ejection control device according to any one of claims 1 to 11, wherein the ejection instruction is performed so as to eject a droplet.
13. The ejection control device according to claim 12, wherein the adjustment unit adjusts the scanning direction of the ejection unit in the predetermined axial direction to be opposite between the first time and the second time. ..
The discharge control device according to any one of claims 1 to 13, wherein the holes are pores or holes formed in the epidermis and a part of the dermis of the skin of a living body.
15. The ejection control device according to claim 1, wherein the first droplets include mesenchymal cells, and the second droplets include epithelial cells.
The ejection control device according to any one of claims 1 to 15, wherein the viscosity of the first droplet is higher than the viscosity of the second droplet.
17. There are a plurality of the holes, and the adjusting section is capable of adjusting the landing positions of the first droplet and the second droplet for each hole, respectively. The discharge control device according to.
A discharge unit that discharges a first droplet and a second droplet containing cells different from each other into one hole opened in the skin of a living body,
An adjusting unit capable of adjusting a landing position of at least one of the first droplet and the second droplet ejected from the ejecting unit in the hole;
A discharge device comprising:
The ejection device according to claim 18, wherein the ejection unit is one of a thermal ink jet head, a piezoelectric ink jet head, an electrostatic ink jet, and a compressed air jet dispenser.
20. The ejection device according to claim 18, wherein the ejection unit has at least two openings capable of ejecting a droplet of 1 to 500 nl to the hole.
19. The ejection unit ejects two droplets so that the second droplet is closer to the opening of the hole than the first droplet in the hole. 21. The discharge device according to any one of claims 20 to 20.
A first discharging step of discharging a first droplet containing mesenchymal cells into one hole opened in the scalp; and, after discharging the first droplet, containing an epithelial cell in the hole A second discharging step of discharging a second droplet;
A discharging method comprising:
A detection step of detecting the position of the hole,
An alignment step of aligning an ejection unit that ejects at least one of the first droplet and the second droplet based on the detected position;
An instructing step of issuing an ejection instruction to the ejection unit,
23. The ejection method according to claim 22, further comprising:
The first discharge step and the second discharge step are performed using any one of a thermal inkjet head, a piezoelectric inkjet head, an electrostatic inkjet, and a pneumatic jet dispenser. The discharge method according to claim 23.
A computer-readable storage medium storing a program that causes a computer to execute each unit of the discharge control device according to claim 1.